The Branch has a long-standing involvement in the systematic evaluation of radiotherapy alone or in combination with chemotherapeutic drugs. As more individuals become long-term cancer survivors, there is greater need to evaluate risk-benefit ratios for various treatment protocols.[unreadable] [unreadable] Secondary Breast Cancer following Hodgkin's Disease[unreadable] To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD, a case-control study of breast cancer was conducted within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger. A radiation dose of 4Gy or more delivered to the breast was associated with a 3.2 fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40Gy (P<.001 for trend). Risk of breast cancer decreased with increasing number of alkylating agent cycles (P=.003 for trend). Risk was also low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses. Additional analyses are underway.[unreadable] [unreadable] Cancer Risks following Bone Marrow Transplantation[unreadable] A case-control study conducted within a cohort of 29,000 recipients of an allogeneic bone marrow transplant found that long-duration of immunosuppressive drug therapy given to treat chronic graft-versus-host disease is strongly associated with increased risk of secondary squamous cell solid cancers, particularly those of the buccal cavity and skin. Risks were highest for patients treated for more than 24 months and those receiving multiple drug regimens including azathioprine.[unreadable] [unreadable] Second Cancer Risks following Retinoblastoma[unreadable] A cohort of 1,600 Retinoblastoma (RB) patients continues to be monitored for cancer risk.Hereditary RB patients continue to be at high risk of sarcoma, melanoma and brain cancer. Radiotherapy further enhances risk of tumors arising in the radiation field. RB patients who have developed melanoma are undergoing clinical examination for dysplastic nevi syndrome, lipomas, and mutations in melanoma susceptibility genes. DNA collected from hereditary RB patients with a second cancer are being genotyped to identify mutations in the RB1 gene that increase susceptibility to a second cancer.[unreadable] [unreadable] Cancer Risks in Family Members of Ataxia-Telangiectasia Patients[unreadable] In collaboration with the Genetic Epidemiology Branch and cancer registries in four Nordic countries, we found that overall cancer incidence was not greater than expected in family members of ataxia-telangiectasia patients. Expansion of the original cohort continues to show that breast cancer risk increased in mothers under age 55, but not other female relatives. An international workshop to combine data from several similar studies is planned.[unreadable] [unreadable] Cancer Mortality and Incidence Risks in Patients with Scoliosis[unreadable] A multi-center retrospective cohort study of 5,573 women who were monitored with diagnostic x-rays for their scoliosis found that they were 70% more likely to die from breast cancer than women in the general population. A statistically significant linear dose-response relationship was observed, with an excess relative risk per Gy of 5.4. A more detailed evaluation of the dose-response relationship and its potential modifying factors is underway.[unreadable] [unreadable] Cancer Incidence Among Patients Undergoing Cerebral Angiography with Thorotrast[unreadable] The Branch recently completed a 40-year follow-up survey of site-specific cancer incidence after cerebral angiography with radioactive Thorotrast.